Microfluidic systems were already the subject of biotechnology research and development in past years and are being used increasingly in the form of so-called lab-on-a-chip systems etc., also for medical diagnosis in point-of-care products. The terms microfluidic system and lab-on-a-chip are used here as synonyms. On these microfluidic chip systems, protocols previously worked out in the laboratory are converted as completely as possible into a microfluidic structure on the lab-on-a-chip, so that the protocols are largely automated and take place with the least possible manual intervention. The chip systems are generally used with operator devices, while the operator devices are outfitted with a holder for the chip as well as electrical, fluidic and actuator interfaces for the chip, if needed.
The microfluidic systems contain various microfluidic structures with size dimensions in the micrometer range, while individual microfluidic structures, especially fluid chambers or fluid reservoirs, can also have larger cross sections in the millimeter range. Often the microfluidic systems are formed by a base plate in which channels and depressions are fashioned, and a cover foil enclosing the channels and depressions. The base plates are molded from plastic by injection molding or embossing and the cover foils are joined fluid-tight to the base plates by gluing or welding. Modular microfluidic systems made of several planar and/or blocklike microfluidic modules are also known, such as the publication of Drese, K.; von Germar, F.; Ritzi, M.: “Sample preparation in Lab-on-a-Chip systems—Combining modules to create a fully integrated system”, in: Medical Device Technology 18 (2007) 1, 42-47. These individual modules are coupled together by suitable connections so as to realize various process pathways, depending on the stated goal.
An often occurring process operation within microfluidic systems is the combining of different fluid volumes. Various solutions already exist for this.
The publication of Götz Münchow, Dalibor Dadic, Frank Doffing, Steffen Hardt, Klaus-Stefan Drese, “Automated chip-based device for simple and fast nucleic acid amplification”, in Expert Rev. Mol. Diagn. 5 (4), (2005), indicates in FIG. 7 and the accompanying description (page 616, left column) a microfluidic structure for the combining of two liquid volumes. The Y-shaped structure for this has two inlet lines coming together at an acute angle, which are joined in a channel. In the region where the inlet lines discharge into the channel the inlet lines are narrowed in cross section. The liquids being combined are introduced into the inlet lines and move by capillary forces as far as the narrowed points of the inlet lines, but halt at the end of these points before entering the channel with the broader cross section. Only when a pressure pulse is applied to at least one inlet line can the capillary force preventing the liquid from moving into the channel be overcome and trigger the combining of the liquids in the channel.
In European patent application EP 1 932 593 A1 a microfluidic structure is indicated for the combining of liquids, in which an inlet line for a first fluid empties into a channel. The first liquid is kept ready in a reservoir joined to the inlet line and open to the surroundings and it flows by capillary forces up to the point where the inlet line empties into the channel. The first liquid is taken up by a second liquid, which is also carried in the channel by capillary forces. Important to this type of fluid control is the correct matching of the capillary forces operating in channel, feed opening and reservoir by structure sizes, as well as surface quality. Furthermore, a ventilation of the reservoir is required.
By microfluidic structures and systems according to the indicated invention are meant those systems and structures whose fluid channels have cross section dimension with magnitudes in at least one direction perpendicular to the direction of flow in the range of 10 μm to 2000 μm and especially preferably in the range of 25 μm to 1500 μm. The liquid volumes stored and delivered in these microfluidic systems and structures are in the nanoliter to several-digit microliter range in the case of small volumes, and in the milliliter range in the case of larger volumes.
Pressure-operable or pressure-operated in the sense of the invention's microfluidic systems or structures means that liquid volumes in the microfluidic systems or structures of the invention are driven or can be driven by a delivery pressure acting from outside the microfluidic system or microfluidic structure, such as one generated by a syringe pump. A passive drive, especially a drive acting solely through capillary forces, is not possible or specified for the microfluidic systems or structures of the invention since the cross sectional dimensions of the microfluidic structures in the microfluidic systems of the invention are so large, at least in sections, or the surface textures of the microfluidic structures are configured such that not enough capillary pressure is formed there for reliable delivery of liquid by the microfluidic systems.
On the other hand, capillary driving of the liquids is also possible in individual sections of the microfluidic systems of the invention.
In alternative embodiments; a driving of liquid volumes by making use of magnetorheological liquids or ferrofluids can also be used in the microfluidic systems or structures of the invention. In this case, plugs of a magnetorheological liquid or a ferrofluid are placed in the direction of flow upstream or downstream of the liquid volumes being delivered in the channels or structures of the microfluidic system. A driving of the plugs and the liquid volumes connected with them is done by magnets moved parallel to the fluid structures. In another variant of this type of propulsion, a plug of a magnetorheological liquid or a ferrofluid is moved in a channel section of larger cross section and produces by its movements a delivery pressure in a channel of smaller cross section, fluidically connected to the former channel. Thanks to the different cross sectional sizes of the channels, a large delivery power can be achieved in the channels of smaller cross section with short displacements of the magnets. In the case of an equally possible reversed relationship of cross sectional sizes, a very position and/or pressure-precise delivery can be achieved in the channels of smaller cross section.